1. Field of Invention
The invention relates to methods and devices for sequencing nucleic acids, including DNA, under tension.
2. Discussion of Related Art
The elastic behavior of nucleic acids such as DNA has been investigated for a variety of purposes and using a variety of techniques. As an example, DNA has been stretched using electrical forces (Schurr et al. Biopolymers 29, 1161-1165 (1990)), electrophoresis (Smith et al. Biopolymers 1990, 1167-73 (1990)), hydrodynamic drag (Chu et al. Science 253, 861-866 (1991); Perkins et al. Science 268, 83-7 (1995); Yanagida et al. Cold Spring Harb Symp Quant Biol 47 Pt 1, 177-87 (1983); van Oijen et al. Science 301, 1235-8 (2003)), magnetic forces (Smith et al. Science 258, 1122-6 (1992)), glass needles (Cluzel et al. Science 271, 792-4 (1996)), optical traps (Smith et al. Science 271, 795-799 (1996); Bustamante et al. Nat Rev Mol Cell Biol 1, 130-6 (2000); Davenport et al. Science 287, 2497-500 (2000); Wuite et al. Nature 404, 103-6 (2000)), and optical tweezers (Wang et al. Biophys. J 72, 1335-1346 (1997)). Data from these studies have provided insights into DNA structure, and have revealed that when stretched by relatively low forces (e.g., less than or equal to 6 picoNewtons (pN)), single stranded DNA (ssDNA) is more compact than double stranded DNA (dsDNA). This difference in compactability is due in part to the shorter persistence length and increased incidence of secondary structure in ssDNA as compared to dsDNA (Kim et al. Nat Meth 4, 397-399 (2007)).